The lab-on-a-chip field is driven by the ability of photolithography to pattern materials at a very high density in a rapid and economical manner. Among many other applications, photolithography has enabled development of electrochemical electrode arrays that can be used, for example, for resolution of spatial gradients of analytes (Pei et al. 2001), measurement of multiple analytes in a sample (Wilson and Nie 2006), or high throughput measurement of transmitter released from individual cells (Amatore et al. 2007; Amatore et al. 2006; Barizuddin et al. 2010; Berberian et al. 2009; Chen et al. 2003; Chen et al. 2007; Dias et al. 2002; Dittami and Rabbitt 2010; Gao et al. 2009; Gao et al. 2008; Hafez et al. 2005; Liu et al. 2011; Sen et al. 2009; Spégel et al. 2007; Spégel et al. 2008; Sun and Gillis 2006). One limitation of electrochemical electrode arrays is that it is often inconvenient to make connections between external amplifiers and hundreds, or potentially even thousands, of electrodes on the device. This is particularly the case if the array device needs to be replaced regularly while performing assays in a high throughput manner.
A similar connectivity issue occurs in other high-density microdevices such as charge-coupled-device cameras or digital memory chips and is resolved using “time-division multiplexing” whereby data originating from multiple elements are sequentially read out using a relatively small number of data lines. In this way the number of external connections can be over a million-fold fewer than the number of elements to be read. Central to this approach are methods to address each data element. For example, if the elements are arranged in a rectangular array, each element can be read using an address consisting of the row and column number of the element.
Time-division multiplexing of electrochemical electrode arrays has been implemented with off-chip multiplexers (Pei, et al. 2001). This reduces the number of external potentiostats required, but the number of connections required to the array is still equal to the number of working electrodes. Thus most of the chip “real estate” is used for making connections rather than serving as sensing elements. True on-chip addressing of electrochemical electrodes was carried out by Fiaccabrino et al., using an NMOS analog multiplexer fabricated on a silicon wafer (Fiaccabrino et al. 1994). However, this application is limited to cases where the electrode array is directly patterned on silicon. Glass is often the preferred substrate for electrochemical electrode arrays because it is inexpensive, has a high shunt resistance and low stray capacitance, and is transparent to allow combination of electrochemical and optical measurements.
Ino et al. recently reported an addressable electrochemical electrode array on a glass substrate where row and column electrodes are patterned in an interdigitated array to allow redox cycling to be activated at individually addressed sensing elements (Ino et al. 2011). This device appears to be limited to applications using redox cycling. In addition, since the array is placed in a single fluid compartment, the effective area of the generator and collector electrodes is larger, and thus the recordings are noisier than if an individual set of microelectrodes is used.